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Inhibitory effects of anti-VEGF antibody on the growth and angiogenesis of estrogen-induced pituitary prolactinoma in Fischer 344 Rats: animal model of VEGF-targeted therapy for human endocrine tumors.

Miyajima K, Takekoshi S, Itoh J, Kakimoto K, Miyakoshi T, Osamura RY - Acta Histochem Cytochem (2010)

Bottom Line: With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group.In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry.Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

ABSTRACT
Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic "blood lakes" in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas.

No MeSH data available.


Related in: MedlinePlus

3D-image analysis using confocal laser scanning microscopy of the pituitary vessels of PRLoma in F344 rats. Infused FITC-gelatin into the anterior pituitary microvessels was used to show the blood flow in the anterior lobe. These images show the control group (A), E2 group (B), and E2+G6-31 group (C). In the control group, fine vascular network structure of the anterior pituitary was seen (A). On the other hand, in the E2 group irregular distension, excessive branching and a segmented pattern and partial loss of vessels were noted (B). In the E2+G6-31 group, decrease in distended and segmented pattern and focal appearance of fine microvessels in the anterior pituitary were clearly observed compared to the control and E2 group (C).
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Figure 7: 3D-image analysis using confocal laser scanning microscopy of the pituitary vessels of PRLoma in F344 rats. Infused FITC-gelatin into the anterior pituitary microvessels was used to show the blood flow in the anterior lobe. These images show the control group (A), E2 group (B), and E2+G6-31 group (C). In the control group, fine vascular network structure of the anterior pituitary was seen (A). On the other hand, in the E2 group irregular distension, excessive branching and a segmented pattern and partial loss of vessels were noted (B). In the E2+G6-31 group, decrease in distended and segmented pattern and focal appearance of fine microvessels in the anterior pituitary were clearly observed compared to the control and E2 group (C).

Mentions: In 3D image analysis using CLSM, the fine vascular network structure of the anterior pituitary was seen in the control group (Fig. 7A). On the other hand, irregular distension, excessive branching and a segmented pattern and partial loss of vessels were frequently observed in the E2 group (Fig. 7B). Compared to the control group and E2 group, decrease in distended and segmented pattern and focal appearance of fine microvessels in the anterior pituitary were clearly observed in the E2+G6-31 group (Fig. 7C).


Inhibitory effects of anti-VEGF antibody on the growth and angiogenesis of estrogen-induced pituitary prolactinoma in Fischer 344 Rats: animal model of VEGF-targeted therapy for human endocrine tumors.

Miyajima K, Takekoshi S, Itoh J, Kakimoto K, Miyakoshi T, Osamura RY - Acta Histochem Cytochem (2010)

3D-image analysis using confocal laser scanning microscopy of the pituitary vessels of PRLoma in F344 rats. Infused FITC-gelatin into the anterior pituitary microvessels was used to show the blood flow in the anterior lobe. These images show the control group (A), E2 group (B), and E2+G6-31 group (C). In the control group, fine vascular network structure of the anterior pituitary was seen (A). On the other hand, in the E2 group irregular distension, excessive branching and a segmented pattern and partial loss of vessels were noted (B). In the E2+G6-31 group, decrease in distended and segmented pattern and focal appearance of fine microvessels in the anterior pituitary were clearly observed compared to the control and E2 group (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875861&req=5

Figure 7: 3D-image analysis using confocal laser scanning microscopy of the pituitary vessels of PRLoma in F344 rats. Infused FITC-gelatin into the anterior pituitary microvessels was used to show the blood flow in the anterior lobe. These images show the control group (A), E2 group (B), and E2+G6-31 group (C). In the control group, fine vascular network structure of the anterior pituitary was seen (A). On the other hand, in the E2 group irregular distension, excessive branching and a segmented pattern and partial loss of vessels were noted (B). In the E2+G6-31 group, decrease in distended and segmented pattern and focal appearance of fine microvessels in the anterior pituitary were clearly observed compared to the control and E2 group (C).
Mentions: In 3D image analysis using CLSM, the fine vascular network structure of the anterior pituitary was seen in the control group (Fig. 7A). On the other hand, irregular distension, excessive branching and a segmented pattern and partial loss of vessels were frequently observed in the E2 group (Fig. 7B). Compared to the control group and E2 group, decrease in distended and segmented pattern and focal appearance of fine microvessels in the anterior pituitary were clearly observed in the E2+G6-31 group (Fig. 7C).

Bottom Line: With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group.In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry.Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

ABSTRACT
Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic "blood lakes" in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas.

No MeSH data available.


Related in: MedlinePlus